Supernatants from human glioblastoma cell lines suppressed in vitro-generated cellular immune responses. These supernatants contained IL-6 but not other cytokines. Short-term incubation of these supernatants with monocytic or dendritic antigen-presenting cells (APC) of healthy individuals resulted in decreased IL-12 and increased IL-10 production. Other GCS-induced changes in these APC include reduced expression of MHC class II and CD80/86. Exposure of monocytes to GCS also prevented their GM-CSF and IL-4-induced differentiation into dendritic cells, and diverted them to macrophages. Therefore, GCS may have the potential for altering the pathway of antigen-presenting cell differentiation.